Investigations in this laboratory have identified and mapped four discrete loci of intracardiac ganglion cells in the rat. More recently, experiments with retrograde tracers demonstrated that different cardiac regions are innervated by specific groups of intracardiac ganglion cells. The objective of the proposed research is to determine whether individual sub-populations of cardiac vagal preganglionic neurons differentially innervate the intracardiac ganglion cells and provide differential control of regional parasympathetic nerve activity and cardiac function. The specific aims are: 1) to determine the anatomical organization of the terminal projections of cardiac vagal preganglionic neurons with anterograde and retrograde tracers, 2) to investigate the neuropeptides and putative neurotransmitters associated with cardiac parasympathetic nerve using immunohistochemistry combined with retrograde tracers, and 3) to test the hypothesis that sub-populations of parasympathetic preganglionic neurons can cause specific regional changes in: a) intracardiac ganglion cell activity, b) cardiac parasympathetic nerve activity, and c) cardiac function. It is proposed to investigate the influence of stimulation of different sub-populations of cardiac vagal preganglionic neurons on: a) intracardiac ganglion cell activity, by accumulation of radiolabeled 2-deoxyglucose in the ganglion cells, b) regional cardiac parasympathetic nerve activity, by measuring regional acetylcholine turnover, and c) indices of cardiac function - heart rate, A-V nodal conduction, and cardiac contractility. The sub-populations of cardiac parasympathetic preganglionic neurons are defined by histological topography (dorsal motor nucleus of the vagus vs nucleus ambiguus), vagus nerve fiber size (B- versus C-fiber) and neuropeptide profile. It is anticipated that stimulation of individual populations of preganglionic neurons will differentially activate specific loci of ganglion cells and be reflected in selective changes in parasympathetic nerve activity and cardiac function. Alterations in parasympathetic cardiac control occur in various pathological states for which there are animal models, such as diabetic neuropathy and cardiomyopathy. Abnormalities of specific populations of neurons, or changes in the differential innervation of the intracardiac ganglion cells, may be contributing factors in the development of the disease. Identification of the relationships between the vagal preganglionic neurons, the intracardiac ganglion cells, and the effector sites in normal animals is fundamental to future investigations of cardiac autonomic dysfunction.